RESUMO
Given increased acceptance of the CoronaVac, there is an unmet need to assess the safety and immunogenic changes of CoronaVac in patients with rheumatic diseases (RD). Here we comprehensively analysed humoral and cellular responses in patient with RD after a three-dose immunization regimen of CoronaVac. RD patients with stable condition and/or low disease activity (n = 40) or healthy controls (n = 40) were assigned in a 1:1 ratio to receive CoronaVac (Sinovac). The prevalence of anti-receptor binding domain (RBD) antibodies and neutralizing antibodies was similar between healthy control (HC) and RD patients after the second and the third vaccination. However, the titers of anti-RBD IgG and neutralizing antibodies were significantly lower in RD patients compared to HCs (p < 0.05), which was associated with an impaired T follicular helper (Tfh) cell response. Among RD patients, those who generated an antibody response displayed a significantly higher Tfh cells compared to those who failed after the first and the second vaccination (p < 0.05). Interestingly, subjects with a negative serological response displayed a similar Tfh memory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-derived peptides as their anti-RBD IgG positive counterpart, and all (4/4) of the non-responders in HCs, and 62.5% (5/8) of the non-responders in patients with RD displayed a positive serological response following the third dose. No serious adverse events were observed. In conclusion, our findings support SARS-CoV-2 vaccination in patients with RD with stable and/or low disease activity. The impaired ability in generating vaccine-specific antibodies in patients with RD was associated with a reduction in Tfh cells induction. The window of vaccination times still needs to be explored in future studies. Clinical trial registration: This trial was registered with ChiCTR2100049138.
Assuntos
COVID-19 , Doenças Reumáticas , Humanos , Anticorpos Neutralizantes , Anticorpos Antivirais , Formação de Anticorpos , Vacinas contra COVID-19 , Imunização , Imunoglobulina G , SARS-CoV-2 , Células T Auxiliares Foliculares , Vacinação , Estudos de Casos e ControlesRESUMO
OBJECTIVE: To identify predictors for lupus low disease activity state (LLDAS), early-achieved LLDAS and long-term disease activity, and to refine a prognostic stratification tool for use in active SLE patients. METHOD: A total of 245 active SLE patients were enrolled, followed up quarterly from 2014 to 2016. LLDAS-50 was defined as the maintenance of LLDAS for ≥50% of the observed time. LLDAS at 3 months after cohort entry (LLDAS-3mo) was considered an early-achieved LLDAS. Multivariate analysis was performed to identify predictors for LLDAS, early-achieved LLDAS and long-term disease activity. Based on the factors associated with LLDAS, a prognostic stratification tool for LLDAS was established. RESULTS: The 2-year probability of achieving LLDAS was 62.9% (154/245). Multivariate analysis-determined renal involvement, haematological involvement and hypocomplementaemia were negative predictors for achieving LLDAS and LLDAS-50. In multivariate logistic analysis, antiphospholipid antibodies positivity, hypocomplementaemia, renal involvement and haematological involvement were identified as negative predictors for achieving LLDAS-3mo. LLDAS-3mo (P < 0.0001; risk ratio: 47.694; 95% CI: 13.776, 165.127) was a strong predictor for LLDAS-50. The probability of achieving LLDAS, LLDAS-50 and LLDAS-3mo were 88.9% (32/36), 69.4% (25/36) and 41.7% (15/36) in the low-risk group, 65% (65/100), 51.0% (51/100) and 32.0% (32/100) in intermediate-risk group, and 52.8% (57/108), 27.8% (30/108) and 13.0% (14/108) in high-risk group respectively. Significant differences (P < 0.0001) were observed in the LLDAS Kaplan-Meier estimates for the three risk groups based on the identified risk factors. CONCLUSION: Renal involvement, haematological involvement and hypocomplementaemia were negative predictors of LLDAS achievement and maintenance. LLDAS-3mo was a positive predictor for the long-term sustainment of LLDAS.
Assuntos
Lúpus Eritematoso Sistêmico , Humanos , Prognóstico , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
OBJECTIVES: To explore the performance of sonoelastography (SE) in diagnosis and clinical evaluation of primary Sjögren's syndrome (pSS). METHODS: SE examination of major salivary glands was conducted for 79 pSS patients, 39 disease controls and 15 healthy subjects. Elastographic images were determined with a qualitative 4-point scoring method. Receiver operating characteristic (ROC) curve was employed to evaluate the performance of the elasticity scoring method and the best cut-off value was determined. The associations between elasticity scores and disease characteristics were analysed to evaluate the clinical value of SE for pSS. RESULTS: Elasticity scores of parotid and submandibular glands in pSS group were significantly higher than those in the non-pSS group (p<0.001). The sum of the scores of all four glands provided the largest AUC-ROC (0.916, 95% CI 0.87-0.962), compared with that of bilateral parotid glands (0.857, 95% CI 0.794-0.919) and that of bilateral submandibular glands (0.783, 95% CI 0.704-0.863). The optimal cut-off value was 9 for combined evaluation of all four glands (81% sensitivity and 87% specificity, respectively). The elasticity scores of parotid glands in patients with disease duration >10 years experienced significant difference as compared to patients with disease duration ≤5 years and 5-10 years respectively (p=0.007, 0.009, respectively), whereas it presented no variations between the disease duration ≤5 years and 5-10 years (p=0.952). CONCLUSIONS: Sonoelastography, performed simultaneously with ultrasonography, is an additional tool for the assessment of the salivary glands in patients with pSS. The elasticity is closely associated with disease duration.
Assuntos
Técnicas de Imagem por Elasticidade , Síndrome de Sjogren , Humanos , Projetos de Pesquisa , Glândulas Salivares/diagnóstico por imagem , Síndrome de Sjogren/diagnóstico por imagemRESUMO
OBJECTIVES: Coronavirus disease 2019 (Covid-19) is outbreaking globally. We aimed to analyse the clinical characteristics, cardiac injury, electrocardiogram and computed tomography (CT) features of patients confirmed Covid-19 and explored the prediction models for the severity of Covid-19. METHODS: A retrospective and single-centre study enrolled 98 laboratory-confirmed Covid-19 patients. Clinical data, electrocardiogram and CT features were collected and analysed using Statistical Package for the Social Sciences software. RESULTS: There were 46 males and 52 females, with a median age of 44 years, categorised into three groups, including mild, moderate and severe/critical Covid-19. The rate of abnormal electrocardiograms in severe/critical group (79%) was significantly higher than that in the mild group (17%) (P = .027), which (r = 0.392, P = .005) positively related to the severity of Covid-19 (OR: 5.71, 95% CI: 0.45-3.04, P = .008). Age older than 60 years old, comorbidities, whether had symptoms on admission, fatigue, CT features, laboratory test results such as platelet count, lymphocyte cell count, eosinophil cell count, CD3+ cell count, CD4+ cell count, CD8+ cell count, the ratio of albumin/globulin decreased and D-dimer, C-reactive protein (CRP), B-type natriuretic peptide (BNP), cardiac troponin I (cTnI) elevated were the risk factors for the increased severity of Covid-19. The logistic model, adjusted by age, lobular involvement score and lymphocyte cell count, could be applied for assessing the severity of Covid-19 (AUC, 0.903; Sensitivity, 90.9%; Specificity, 78.1%). CONCLUSIONS: Age >60 years old, chronic comorbidities, lymphocytopoenia and lobular involvement score were associated with the Covid-19 severity. The inflammation induced by Covid-19 caused myocardial injury with elevated BNP and cTnI level and abnormal electrocardiograms.
Assuntos
COVID-19 , Adulto , China , Feminino , Humanos , Contagem de Leucócitos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2 , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: To explore the family-centred postoperative care of congenital heart disease (CHD) patients. METHODS: A total of 200 child patients with Congenital Heart Disease and their families were selected as the research objects in the study. All the research objects were divided into intervention group and control group, with 100 of them in each group. Based on the current development of the family-centred postoperative care, the paper employed the Delphi Method to construct the contents of family-centred postoperative care and educated the parents with the contents. Later by assessing the left ventricular ejection fraction (LVEF), the oxygen saturation, and the New York Heart Association (NYHA) functional classification of the child patients, it was seen that the postoperative pain of patients in the intervention group was more effectively relieved along with a faster recovery of cardiac functions compared to the control group. RESULTS: The results showed that the absence of parental care was the major stressor for the child patients. For the parents, the lack of knowledge on CHD and its therapy was the source of anxiety. CONCLUSIONS: Family-centred postoperative care promoted the communications between doctors and parents of child patients, relieved the postoperative pain of the patients and the psychological trauma of their families. The child patients were provided with a better medical environment, which helped in a faster recovery.
Assuntos
Enfermagem Familiar , Cardiopatias Congênitas , Criança , Cardiopatias Congênitas/cirurgia , Humanos , Pais , Volume Sistólico , Função Ventricular EsquerdaRESUMO
BACKGROUND: This study aims to investigate the related factors for the retention time of tracheobronchial foreign bodies in infants and children, to provide help for the assessment of the disease, surgical risk, and prognosis. MATERIALS AND METHODS: The clinical data of 1060 patients with tracheobronchial foreign bodies from January 2015 to December 2015 were retrospectively studied, and the correlation of the retention time of foreign bodies with age, gender, preoperative complications, granulation formation, operation time, and hospital stay was analyzed. RESULTS: The retention time of foreign bodies was not correlated with age (r = 0.041, P = 0.194) and gender (r = 0.039, P = 0.214) but was correlated with preoperative complications (r = 0.072, P = 0.023), granulation formation (r = 0.134, P < 0.001), operation time (r = 0.112, P < 0.001), and hospital stay (r = 0.189, P < 0.001). CONCLUSIONS: The retention time of foreign bodies was closely correlated with granulation formation, preoperative complications, operation time, and hospital stay.
Assuntos
Brônquios/lesões , Corpos Estranhos/cirurgia , Tempo para o Tratamento/estatística & dados numéricos , Traqueia/lesões , Brônquios/cirurgia , Broncoscopia , Criança , Pré-Escolar , Feminino , Corpos Estranhos/complicações , Corpos Estranhos/diagnóstico , Humanos , Lactente , Tempo de Internação/estatística & dados numéricos , Masculino , Duração da Cirurgia , Período Pré-Operatório , Estudos Retrospectivos , Distribuição por Sexo , Fatores de Tempo , Traqueia/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: Sudden cardiac death (SCD) induced by malignant ventricular tachycardia (MVT) among young adults with right ventricular cardiomyopathy/dysplasia (ARVC/D) is a devastating event. Parts of ARVC/D patients have a mutation in genes encoding components of cardiac desmosomes, such as desmoglein-2 (DSG2), plakophilin-2 and desmoplakin. CASE PRESENTATION: Here we report a potentially pathogenic mutation in the DSG2 gene, which was identified in a family with ARVC/D using Whole Exome Sequencing (WES) and Sanger Sequencing. In all, Patient III:1 with ARVC/D carried the compound heterozygous mutations of DSG2 p.F531C and KCNE5 p.D92E/E93X, which were both inherited from her mother (II:2), who died of SCD. Carriers of DSG2p.F531C showed various phenotypes, such as ARVC/D, SCD, MVT and dilated cardiomyopathy. For III:1, there were significant low-voltage regions in the inferior-apical, inferior-lateral wall of the right ventricular epicardium and outflow tracts of the right ventricle. Under the guidance of a three-dimensional mapping system, MVT was successfully ablated with an epicardial-endocardial approach targeting for late, double or fragmental potentials after implantable cardioverter-defibrillator (ICD) electrical storms. No VT recurrence was observed during the one year of follow-up. CONCLUSIONS: When coexisting with heterozygous KCNE5 p.D92E/E93X, heterozygous DSG2 p.F531C as a genetic background was found to predispose to ARVC/D, SCD and MVT, which were successfully ablated using an epicardial-endocardial approach.
Assuntos
Displasia Arritmogênica Ventricular Direita/complicações , Morte Súbita Cardíaca/etiologia , Morte Súbita/etiologia , Desmogleína 2/genética , Mutação/genética , Canais de Potássio de Abertura Dependente da Tensão da Membrana/genética , Adulto , Displasia Arritmogênica Ventricular Direita/genética , Feminino , Heterozigoto , Humanos , MasculinoRESUMO
OBJECTIVE: This study aimed to identify the pathogenic mutation in a Chinese family with unexplained sudden death (USD) or occasional syncope. MATERIALS AND METHODS: Whole exome sequencing and target capture sequencing were respectively conducted for two related patients. The genetic data was screened using the 1000 genomes project and SNP database (PubMed), and the identified mutations were assessed for predicted pathogenicity using the SIFT and Polyphen-2 algorithms. RESULTS: We identified a heterozygous mutation in the RYR2 gene at c.490C>T (p.P164S), highly conserved across all species, in three family members of USD, syncope and malignant ventricular tachycardias induced by treadmill exercise test, while another heterozygous de novo mutation in SCN5A at c.5576G>A p.R1859H was detected in one family member. Both variants were verified by Sanger sequencing. Importantly, RYR2 p.P164S is associated with the risk of sudden cardiac death, such as in catecholaminergic polymorphic ventricular tachycardia. CONCLUSIONS: A pathogenic mutation in RYR2 (p.P164S) is the likely cause of USD in a Chinese family associated with malignant ventricular arrhythmias. Whole exome and target capture sequencing can be useful for discovering the genetic causes of USD.
Assuntos
Morte Súbita Cardíaca , Sequenciamento do Exoma , Mutação/genética , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Adolescente , Adulto , Idoso , Algoritmos , Povo Asiático , Criança , Teste de Esforço , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Síncope/genéticaRESUMO
BACKGROUND: There is still a lack of data on blood lead levels (BLLs) and blood lead levels (BLLs) in healthy children of all ages from 0 to 18 years in China. This study was performed to analyze the BLLs and BCLs in healthy children aged 0-18 years from 2017 to 2022 in urban and rural areas of Henan Province, Central China, as well as their relationships with socio-demographic variables and certain relevant exposure factors. To provide a basis for evaluating public health policy development and exposure risk management. METHODS: This was an observational study containing data from 17 prefecture-level cities in Henan, China. Blood Pb and Cd levels were determined using a triple quadrupole inductively coupled plasma mass spectrometer equipped with an autosampler. We first calculated the concentrations of Pb and Cd elements in participants of different genders, ages and years, and then created visual graphs depicting the distribution of each element in terms of gender, age and year (2017-2022). The rates between different groups were compared using the Chi-square test or Fisher exact test (if applicable). The means were compared by one-way ANOVA, medians were compared with the Kruskal-Wallis rank-sum test. Generalized linear models (GLM) were performed to estimate the effects of various factors on blood Pb and Cd concentrations in children. RESULTS: We recruited a total of 25,920 children (16,142 boys and 9,778 girls) aged 0.01 to 18.00 years (2.58 (1.00,6.25)). The median of BLLs was 23.48µg/L, around 9.39% of studied children had elevated BLLs. The median of BCLs was 0.66µg/L, around 1.84% of studied children had elevated BCLs. The median blood Pb concentration was higher in boys (23.90µg/L) than in girls (22.75µg/L) (P<0.001). The median blood Pb concentration was highest in the 3-7 years group (24.51µg/L) and the median blood Cd concentration was highest in the 1-3 years group (0.66µg/L) among all age groups. Both BLLs and BCLs were substantially higher in children in 2020-2022 compared to 2017-2019. Rural children had lower BLLs and higher BCLs. The results of the generalized linear model showed that children in households using Oil, coal, pellet or other wood as a fuel for heating, children with higher frequency of exposure to tobacco smoke and beverage intake had significantly increased chances of elevated BLLs and BCLs. CONCLUSIONS: Pb and Cd exposure of children in this area is relatively low, but associated risk factors continue to exist in vulnerable populations. This study is the first big data analysis of Pb and Cd in children in Henan, China, and provides baseline information for future research.
Assuntos
Cádmio , Chumbo , Criança , Feminino , Humanos , Masculino , China , Cidades , Exposição Ambiental , Fatores de Risco , Recém-Nascido , Lactente , Pré-Escolar , AdolescenteRESUMO
PURPOSE: To study the clinicopathological variables connected with disease-free survival (DFS) as well as overall survival (OS) in patients who are ER-positive or HER2-negative and to propose nomograms for predicting individual risk. METHODS: In this investigation, we examined 585 (development cohort) and 291 (external validation) ER-positive, HER2-negative breast cancer patients from January 2010 to January 2014. From January 2010 to December 2014, we retrospectively reviewed and analyzed 291 (external validation) and 585 (development cohort) HER2-negative, ER-positive breast cancer patients. Cox regression analysis, both multivariate and univariate, confirmed the independence indicators for OS and DFS. RESULTS: Using cox regression analysis, both multivariate and univariate, the following variables were combined to predict the DFS of development cohort: pathological stage (HR = 1.391; 95% CI = 1.043-1.855; P value = 0.025), luminal parting (HR = 1.836; 95% CI = 1.142-2.952; P value = .012), and clinical stage (HR = 1.879; 95% CI = 1.102-3.203; P value = 0.021). Endocrine therapy (HR = 3.655; 95% CI = 1.084-12.324; P value = 0.037) and clinical stage (HR = 6.792; 95% CI = 1.672-28.345; P value = 0.009) were chosen as predictors of OS. Furthermore, we generated RS-OS and RS-DFS. According to the findings of Kaplan-Meier curves, patients who are classified as having a low risk have considerably longer DFS and OS durations than patients who are classified as having a high risk. CONCLUSION: To generate nomograms that predicted DFS and OS, independent predictors of DFS in ER-positive/HER2-negative breast cancer patients were chosen. The nomograms successfully stratified patients into prognostic categories and worked well in both internal validation and external validation.
Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Prognóstico , Estudos Retrospectivos , Receptor ErbB-2 , Intervalo Livre de DoençaRESUMO
Introduction: Transmembrane protein 65 (TMEM65) is an inner mitochondrial membrane protein, which played important role in mediating autophagy, smooth muscle contraction, protein glycosylation, and immune response. In recent years, the interest had risen for exploring the function of the TMEM genes in the cancer fields. As a consequence, in our pan-cancer research of the TMEM65, we explored the function of the gene in kinds of database and tried to apply the finding in the clinical practice. Methods: In this research, we provide a comprehensive investigation of TMEM65 expression in a pan-cancer manner containing 33 cancer types. We evaluated the association of TMEM65 with the prognosis, immune infiltration, drug sensitivity analysis, GSVA enrichment analysis, TMB, MSI, NEO, and hotspot mechanisms. Results: TMEM65 was abnormally expressed in 24 types of cancers and showed correlation with the OS for 6 cancers and PFI for 9 cancers and kpI for 3 types. Moreover, the TME score, CD8 T effector, and immune checkpoint scoring systems showed a close correlation with the TMEM65. Moreover, TMEM65 was strongly correlated with some of the most common tumor-related genes and certain pathways (TGF beta signaling, TNFA signaling, hypoxia, pyroptosis, DNA repairing, autophagy, ferroptosis, and other related genes). Additionally, the TMEM65 showed correlations with the tumor mutational burden (TMB), microsatellite instability (MSI), NEO, and drug sensitivity. Finally, we confirmed several pathways by the GSEA and GSVA for the TMEM65 at the breast cancer aspects. Nomogram prediction model was also established for the breast tumors based on the TMEM65 level and other variables. Conclusion: Above all, the TMEM65 played important roles in predicting the prognosis of the cancers and correlated with the tumor immunity in the pan-cancer analysis.
RESUMO
BACKGROUND: Galectins (LGALS) are a family of carbohydrate-binding proteins, and LGALS family members have shown prognostic roles in various types of cancers. However, the prognostic significance of some LGALS family members has not been studied in breast malignancy. METHODS: The prognostic value of LGALS family mRNA expression in breast cancer patients was investigated according to distinct clinicopathological features (including lymph node, intrinsic subtype, pathological grade, HER2, and TP53 status) using the Kaplan-Meier plotter database. Quantitative real-time polymerase chain reaction and western blotting were used to detect the mRNA and protein expression of LGALS in breast cancer and normal breast cells. The aberrant expression of specific LGALS and its correlation with breast cancer outcomes remains elusive. In the present analysis, we comprehensively explored an immunohistochemistry-based map of protein expression profiles in normal tissues, cancer, and cell lines from the widely available Human Protein Atlas (HPA) database. Immunohistochemistry was applied to evaluate the expression of LGALS between cancer and normal tissues. RESULTS: Our results showed that overexpression of LGALS2 mRNA were correlated with satisfactory overall survival among all breast cancer patients. Furthermore, LGALS2 and LGALS4 expression correlated with a better overall survival (OS) in grade III breast cancer patients; LGALS2 also predicted a better OS in basal-like subtype patients, luminal B patients, HER2-overexpressing patients, TP53 mutated and wild breast cancer patients. Notably, the mRNA and protein expression levels of LGALS2 were decreased in cancer cells compared with normal cells (P<0.05). Furthermore, LGALS2 expression in immunostaining score was lower in cancer tissues than in normal tissues (P<0.005). CONCLUSION: In conclusion, LGALS2 has potential as a valuable biomarker for envisaging a satisfactory prognosis in patients with breast tumours, particularly those with luminal and basal B types, all stages and grade III tumours.
RESUMO
OBJECTIVES: Detailed analysis targeting B cell subgroups was considered crucial in monitoring autoimmune diseases and treatment responses. Thus, precisely describing the phenotypes of B cell differentiation and their variation in primary Sjögren's syndrome (pSS) is particularly needed. METHODS: To characterize the proportions and absolute counts of B cell subsets, peripheral blood from 114 healthy adults of China (age range: 19-73 years) and 55 patients with pSS were performed by flow cytometry and CD19, CD20, CD24, CD27, CD38 and IgD were used as surface markers to identify B cell mature process. Age- and gender-stratified analyses were then carried out to improve the interpretation of B cell subsets. RESULTS: The assessments from healthy adults showed that the proportion of naive B cells presented a significant increase with age. A reversal trend was noted that the percentage of B10 decreased markedly with age. In addition, analysis based on gender showed that the relative percentage and number of naive B cells were higher in females than in males whereas the proportions of switched memory B cells and B10 cells were decreased in female. Patients with pSS exhibited a significant expansion in naïve B cells and unswitched memory B cells, accompanied with decreased switched memory B cells and B10 cells, which were identified to be associated with autoantibody production. CONCLUSIONS: Our study presented a reliable analysis by flow cytometry to cover the principal B cell subtypes. These different stages of B lymphocytes may have implications for evaluating the activation of pSS and other autoimmune diseases and treatment efficacy.KEY MESSAGESB cell subsets play a pivotal role in the pathogenesis of primary Sjögren's syndrome (pSS) and other autoimmune diseases. A practical and accurate flow cytometry method to profile B cell phenotypes in peripheral blood of healthy adults is especially essential.Additionally, we presented reliable reference ranges for B cell subsets in regards to the local population. Age- and gender-related analyses are available to better understand their influence in immune status and treatment outcome.The distribution of B-cell subsets is found substantially altered in patients with pSS, bringing novel avenues for pSS research in the future.
Assuntos
Doenças Autoimunes , Subpopulações de Linfócitos B , Síndrome de Sjogren , Doenças Autoimunes/metabolismo , Subpopulações de Linfócitos B/metabolismo , Subpopulações de Linfócitos B/patologia , Linfócitos B/metabolismo , Linfócitos B/patologia , Feminino , Citometria de Fluxo , Humanos , MasculinoRESUMO
Objective: This study aimed to examine the prevalence and the related risk factors of congenital heart disease (CHD) in children with different birth weights in China and the relationship between the subtypes of CHD and birth weight (BW). Methods: This study conducted a cross-sectional survey on the data collected in the children's congenital heart disease database (CHDD) established in China. This database contained data from one Grade A, Level III Children's Public Hospital in Zhengzhou, Henan. The study included all the children and their parents in the database from 2014 to 2020 as the study subjects, and the missing data were processed by means of imputation. Diagnoses of CHD were coded using the International Classification of Diseases version 10 (ICD-10), and subtypes were classified by the codes Q20 to Q26. We reported the prevalence of CHD based on birth weight and gestational age and analyzed the related risk factors for children with CHD in different birth weight groups and factors for children of the same birth weight groups between the CHD groups and the non-CHD groups. The generalized linear model was used to assess the association between the subtypes of CHD and BW by establishing three adjusting models, and the data were stratified for further analysis by urban-rural and infant gender. Results: A total of 42,814 children were identified as having CHD among 5,071,799 live children; the overall prevalence of CHD was 8.44 per 1,000 live births during 2014-2020; and the three subtypes with the highest prevalence of CHD were atrial septal defect (ASD) (2.75), ventricular septal defect (VSD) (2.57), and patent foramen ovale (PFO) (1.12). The prevalence of CHD was 18.87 in the group with BW <1,500 g, 12.84 in the group with BW 1,500-2,500 g, 8.24 in the group with BW 2,500-4,000 g, and 4.80 in the group with BW ≥4,000 g. The prevalence of CHD was 16.62 in the small for gestational age (SGA) group, 6.99 in the appropriate for gestational age (AGA) group, and 6.40 in the larger for gestational age (LGA) group. Parental factors such as drinking, smoking, viral infections, peri-pregnancy exposure to radioactive substances, low family monthly expenditure, and low Apgar scores at 1 and 5 min were related to the increased risk of CHD in the offspring. Parental supplementation of folic acid and exercise during the peri-pregnancy period could reduce the risk of CHD in the offspring. The results of Model 3 adjusting for confounding variables showed that infants with ASD had a birth weight 461 g lower (95% CI: -1,085, -128), infants with VSD had a birth weight 426 g lower (95% CI: -932, -120), infants with tetralogy of Fallot (TOF) had a birth weight 532 g lower (95% CI: -987, -168), and without classification, infants with CHD had a birth weight 973 g lower (95% CI: -1,502, -204). Conclusion: In very low birth weight (VLBW) and low birth weight (LBW) infants, CHDs are more prevalent than in the general live-born population. Moreover, some peri-pregnancy factors of parents are closely related to the occurrence of CHD in offspring; different types of heart defects can lead to LBW. Therefore, if the fetus is found to have a heart defect during the prenatal examination, the mother should pay more attention to maintaining weight and ensuring that the fetus is within the normal weight range, thereby increasing the postpartum survival rate, reducing complications, and promoting children's health.
RESUMO
Objective: This study explores the factors influencing death anxiety in patients with advanced cancer, and to investigate the role of family function on death anxiety, and the correlation between meaning in life and death anxiety. Methods: Patients with advanced cancer who were hospitalized in three institutions from November 2020 to May 2021 were recruited in this cross-sectional study. The Chinese version of the Death and Dying Distress Scale, Meaning in Life Scale For Advanced Cancer Patients and Family APGAR Index were used to assess death anxiety, meaning in life and family function. Pain symptoms were evaluated by the Numeric Rating Scale. Karnofsky Performance Status, patients' socio-demographic and clinical variables were also recorded. Statistical analyses were performed using IBM SPSS Statistics for Windows (version 26.0). Multivariate regression analysis was performed to examine the correlations of social-demographic and clinical variables with family function and death anxiety. Results: Three hundred and twenty-eight patients with advanced cancer were included in this study. The results showed that 12.2% of patients experienced moderate to severe death anxiety. Meaning in Life Scale For Advanced Cancer Patients (acceptance of death, controlling one's life), types of institution (oncology department of tertiary hospitals), self-perceived economic burden (extreme), Karnofsky Performance Status score, age, and medical insurance status (self-paid, inter-provincial medical insurance) were identified as associated factors of death anxiety (R 2 â= â0.335, F â= â20.072, P â< â0.001). Patients with good family function scores had significantly low level of death anxiety in univariate analysis (F â= â5.892, P â= â0.003). Multivariate analysis revealed no significant association between family function and death anxiety. Conclusions: Our results demonstrated that the oncology department of a tertiary hospital, extremely high of self-perceived economic burden, self-pay, and inter-provincial medical insurance might be associated with higher death anxiety in patients with advanced cancer. Lower level death anxiety was associated with higher level acceptance of death, a greater sense of life control, better physical performance, and older age. Further confirmation about the association between family function and death anxiety in patients with advanced cancer is warranted in the future.
RESUMO
Sjögren's syndrome (SS) is a systemic autoimmune disease with no efficient treatment, and it is associated with dysregulated immune cells and impaired interleukin (IL)-2 signaling. IL-2 is critical for the development and maintenance of Treg cells. The use of low dose of IL-2 (LDIL-2) in the treatment of autoimmune diseases is promising, but the efficacy and mechanism in SS therapy are still to be confirmed. This study aims to investigate the therapeutic effect of LDIL-2 on SS in NOD (non-obese diabetic) mice. NOD mice (female, 8 weeks old) were randomly assigned into three groups (n = 8). Low dose of IL-2 (LDIL-2), high dose of IL-2 (HDIL-2), and isometric sterile water (control) were administered subcutaneously daily from week 8 to week 16. LDIL-2 administration significantly recovered the reduction in saliva flow and suppressed lymphocyte inflammation of the submandibular glands (SMGs) when compared with those treated with sterile water as controls (p < 0.05). SS related biomarkers including ANA, Anti-SSA/Ro, and Anti-SSB/La also declined (p < 0.05). In the low dose of IL-2 treated group, the proportion of CD4+CD25+Foxp3+Tregs in both spleen and cervical-lymph-node were higher than control mice (p < 0.05). Furthermore, CD4+Bcl-6+PD-1+CXCR5+Tfh cells, CD4+IFN-γ+Th1 cells, and CD4+IL-17A+Th17 cells were significantly reduced in LDIL-2 group (p < 0.05). Analysis of the SMGs biopsies showed significantly decreased inflammation scores after LDIL-2 administration and an increase of Tregs with immunohistochemical staining. Our findings provide in vivo evidence that LDIL-2 was an effective therapeutic intervention for SS observed in NOD mice and may restore immune balance through the promotion of Treg and suppression of germinal center (GC) B cells and effector T cells.
RESUMO
The imbalance between pathogenic and beneficial species of the intestinal microbiome and metabolism in rheumatoid arthritis (RA) remains unclarified. Here, using shotgun-based metagenome sequencing for a treatment-naïve patient cohort and a "quasi-paired cohort" method, we observed a deficiency of butyrate-producing species and an overwhelming number of butyrate consumers in RA patients. These outcomes mainly occurred in patients with positive ACPA, with a mean AUC of 0.94. This panel was also validated in established RA with an AUC of 0.986 in those with joint deformity. In addition, we showed that butyrate promoted Tregs, while suppressing Tconvs and osteoclasts, due to potentiation of the reduction in HDAC expression and down-regulation of proinflammatory cytokine genes. Dietary butyrate supplementation conferred anti-inflammatory benefits in a mouse model by rebalancing TFH cells and Tregs, as well as reducing antibody production. These findings reveal the critical role of butyrate-metabolizing species and suggest the potential of butyrate-based therapies for RA patients.
Assuntos
Artrite Reumatoide , Microbioma Gastrointestinal , Animais , Anti-Inflamatórios/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Butiratos/uso terapêutico , Humanos , Camundongos , Linfócitos T Reguladores/metabolismoRESUMO
Importance: Primary Sjögren syndrome (pSS) is a systemic autoimmune disease associated with dysregulated immune cells, with no efficient therapy. There is a need to study potential therapeutic approaches. Objective: To investigate the efficacy, safety, and immune response of low-dose interleukin 2 (LD-IL-2) in the treatment of pSS. Design, Setting, and Participants: A double-blind, placebo-controlled randomized clinical trial was conducted with a 2-group superiority design from June 2015 to August 2017. Sixty patients, aged 18 to 70 years, were recruited from Peking University People's Hospital. Efficacy analyses were based on the intention-to-treat (ITT) principle. Data were analyzed from December 2018 to March 2020. Interventions: Patients with pSS were treated with LD-IL-2 or placebo for 12 weeks and accompanied by 12 weeks of follow-up. Main Outcomes and Measures: The primary end point was defined as a 3-point or greater improvement on the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) by week 24. The secondary end points included other clinical responses, safety, and changes of immune cell subsets at week 12 and 24. Results: Sixty patients with pSS were recruited, with 30 in the LD-IL-2 group (mean [SD] age, 47.6 [12.8] years; 30 [100%] women) and 30 in the placebo group (mean [SD] age, 51.0 [11.9] years; 30 [100%] women), and 57 completed the trial. More patients in the LD-IL-2 group (20 [66.7%]) achieved ESSDAI score reduction of at least 3 points than in the placebo group (8 [26.7%]) at week 24 (P = .004). There were greater resolutions of dryness, pain, and fatigue in the LD-IL-2 group than placebo group at week 12 (dryness: difference, -18.33 points; 95% CI, -28.46 to -8.21 points; P = .001; pain: difference, -10.33 points; 95% CI, -19.38 to -1.29 points; P = .03; fatigue: difference, -11.67 points; 95% CI, -20.65 to -2.68 points; P = .01). No severe adverse events were observed in either group. In addition, the LD-IL-2 group showed a significant decrease in infection compared with the placebo group (1 [3.3%] vs 9 [30.0%]; P = .006). Immunological analysis revealed that LD-IL-2 promoted an expansion of regulatory T cells and regulatory CD24highCD27+ B cells. Conclusions and Relevance: In this randomized clinical trial, LD-IL-2 was effective and well tolerated in patients with pSS, and it restored immune balance, with enhanced regulatory T cells and CD24highCD27+ B cells. Trial Registration: ClinicalTrials.gov Identifier: NCT02464319.
Assuntos
Síndrome de Sjogren , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Síndrome de Sjogren/tratamento farmacológico , Síndrome de Sjogren/complicações , Interleucina-2/uso terapêutico , Método Duplo-Cego , Resultado do Tratamento , Fadiga/tratamento farmacológico , Dor/complicaçõesRESUMO
Focus on form has been extensively studied in text-based online dyadic chats but much less has been explored in group chats with interlocutors from different language backgrounds. Additionally, there are very few studies investigating covert focus on form. This study investigated the effects of interlocutor types on errors and focus on form episodes, both covert and overt, in text-based online group chats. We collected chat logs from two collaborative online international learning projects. One project was developed for the collaboration between an English course at a Chinese university and an art history course at a U.S. university; the other between another cohort of the same English course and a cultural studies course at a Mexican university. We compared errors, feedback, and other characteristics of focus on form episodes between the two projects. Analyses revealed significant differences in characteristics such as overtness (overt, covert), linguistic focus (mechanical, lexical, and grammatical), and source (code, message). However, no significant differences were found for the type of focus on form (preemptive, reactive), presence of uptake, uptake quality (successful, unsuccessful), and repair provider (self, other). Students showed a preference for self-repair over other-repair and for lexical focus over mechanical and grammatical foci in both projects. Overall, only a small proportion of errors were followed by feedback. Therefore, a small amount of uptake and successful uptake occurred in both projects. The results can shed light on how instructors could provide effective scaffolding and tasks to make virtual exchange projects more rewarding.
RESUMO
INTRODUCTION: Low-dose interleukin-2 (IL-2) selectively restores disturbances of regulatory T cells (Treg) and conventional T cells, resulting in the induction of remission in patients with systemic lupus erythematosus. However, to date no research has been carried out on the efficacy of low-dose IL-2 in the treatment of refractory lupus nephritis (LN). The aim of the study reported here was to investigate the renal response to low-dose IL-2 in patients with refractory LN. METHODS: The study population comprised ten patients with refractory LN who failed to achieve complete response or who had relapsed while being treated with at least two conventional immunosuppressive agents. One treatment cycle consisted of IL-2 at a dose of 1 million IU administered subcutaneously every other day for 2 weeks followed by a 2-week break. All patients received three cycles of IL-2 and were then followed up for another 12 weeks without any increase in the dose of previous immunosuppressive agents and steroids. RESULTS: Of the ten patients enrolled in the study, seven (70%) achieved ≥ 50% improvement in proteinuria at 12 weeks after initiating treatment with IL-2. Median proteinuria was significantly reduced by 50.3% at week 12, from 1.83 (interquartile range [IQR] 1.23-3.21) g/24 h at baseline to 0.91 (IQR 0.52-1.60) g/24 h at 12 weeks (P = 0.005). This was accompanied by a 71% reduction in urine erythrocytes, from 64/µl (IQR 24-102/µl) at baseline to 18/µl (IQR 2-20/µl) at 12 weeks (P = 0.018). Anti-dsDNA was decreased from 27.9 (IQR 7.6-40.28) IU/ml at baseline to 14.1 (IQR 7.3-20.12) IU/ml (P = 0.021) at week 12, while complements C3 and C4 were slightly increased (P = 0.445, P = 0.241, respectively). A significant expansion of Treg cells, from 9.3% at baseline to 16.6% at 12 weeks, was also found (P < 0.05). No serious adverse events occurred during the treatment period. CONCLUSIONS: Low-dose IL-2 therapy may have a promising role in the treatment of refractory LN as an alternative and safe therapeutic approach. It may be used as multi-target combination therapy in clinical practice.